No abstract available.
Testis*

OBJECTIVE: To estimate the effect of maternal age on obstetric outcomes, a retrospective analysis was done. METHODS: Twenty six hundred and forty six women who delivered a singleton baby at our hospital from January 1, to December 31, 2004 were enrolled in this study. Subjects were divided into 3 age groups; 1) less than 35 years, 2) 35-39 years, and 3) 40 years and older. Chi-square test was used to assess the effect of age on obstetrics outcome. Then the odds ratio was calculated to represent clinically meaningful risk. RESULTS: A total of 2646 women with complete data were available; 2245 (84.9%) less than 35 years of age; 350 (13.2%) 35-39 years; and 51 (1.9%) 40 years and older. Increasing age was significantly associated with chromosomal abnormalities (OR 3.9and 8.8 for ages 35-39 years and age 40 years and older, respectively), Preterm premature rupture of membranes (OR 1.3 and 3.2) and cesarean delivery (OR 2.0 and 5.5). Patients aged 35-39 years were at increased risk for placenta previa (OR 1.8) and congenital anomaly (OR 2.8) but these were not statistically significant. The rate of the preterm delivery was increased by age (OR 1.3 and 1.9 for ages 35-39 years and age 40 years and older, respectively) but it was not statistically significant (p=0.121). We did not find advanced maternal age to be associated with a statistically increased risk for preeclampsia, congenital anomaly, gestational diabetes, placenta abruption, low birth weight, macrosomia, neonatal morbidity (NICU admission), and perinatal loss. CONCLUSION: In conclusion, although the likelihood of adverse outcomes increases with maternal age, patients and obstetric care providers can be reassured that overall maternal and fetal outcomes are favorable in this patient population.
Chromosome Aberrations ; Diabetes, Gestational ; Female ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Maternal Age ; Membranes ; Obstetrics ; Odds Ratio ; Placenta ; Placenta Previa ; Pre-Eclampsia ; Pregnancy ; Pregnancy Outcome* ; Pregnancy* ; Retrospective Studies ; Rupture

Isolation of induced pluripotent stem cells (iPSCs) from fully differentiated somatic cells has revolutionized existing concepts of cell differentiation and stem cells. Importantly, iPSCs generated from somatic cells of patients can be used to model different types of human diseases. They may also serve as autologous cell sources that can be used in transplantation therapy. In this study, we investigated the neuronal properties of an iPSC line that is derived from human neonatal foreskin fibroblasts (FS-1). We initially examined the morphology and marker expression of FS-1 cells at undifferentiated stage. We then spontaneously differentiated FS-1 cells in suspension culture and examined the expression of markers representing three germ layers. We finally differentiated FS-1 cells into neuronal lineages by co-culturing them with PA6 stromal cells, and found that, under the conditions we used, they have a tendency to differentiate into more forebrain-type neurons, suggesting that FS-1 iPSC-derived neural cells will be useful to be used in cell therapy of stroke or Huntington's disease, among others. Taken together, FS-1 cells derived from human neonatal fibroblasts exhibit very similar properties with human ES cells, and can provide useful sources for cell therapy and various other applications.
Cell Differentiation ; Fibroblasts ; Foreskin ; Germ Layers ; Humans ; Huntington Disease ; Induced Pluripotent Stem Cells ; Infant, Newborn ; Neurons ; Pluripotent Stem Cells ; Stem Cells ; Stroke ; Stromal Cells ; Tissue Therapy ; Transplants

Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that CYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their inter-assay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure CYP induction, we determined CYP induction by using luminescent assay. Luminescent CYP assays link CYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of CYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and mosapride citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while mosapride citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent CYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent CYP assays decrease the interference between the optical properties of the test compound and the CYP substrates. Therefore, luminescent CYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput CYP screening during early drug discovery.
Citric Acid* ; Colitis ; Cytochrome P-450 CYP1A2 ; Cytochrome P-450 Enzyme System* ; Cytochromes* ; Drug Discovery ; Enzyme Induction* ; Fireflies ; Hepatocytes ; Humans* ; Isoenzymes ; Liver ; Luciferases ; Luminescence ; Luminescent Measurements* ; Mass Screening ; Mesalamine* ; Metabolism ; RNA, Messenger

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 muM in patch clamp assay and increased the heart rate and blood pressure (76 Deltabpm in heart rate and 51 DeltammHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 muM and 30 muM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.
Action Potentials ; Animals ; Blood Pressure ; Cardiovascular System ; Counterfeit Drugs ; Dogs ; Heart Rate ; HEK293 Cells ; Inhibitory Concentration 50 ; Pharmaceutical Preparations ; Pharmacology* ; Purkinje Fibers ; Rabbits ; Telemetry

BACKGROUND/AIMS: In order to identify microsatellite instability (MSI), the test based on the polymerase chain reaction (PCR) can be used. However, PCR is not routinely performed in all hospital laboratories. Recently, immunohistochemistry (IHC) for MLH1 and MSH2 proteins has been reported as a rapid and useful method for MSI. However, the efficacy of IHC in the detection of the MSI has not been well established. The aim of this study was to evaluate the usefulness of IHC in the detection of the MSI by comparing it with the test results using PCR in colorectal cancer (CRC). METHODS: Paraffin-embedded normal and tumor tissues from seventy-five patients who underwent surgical resection of CRC were used. Abnormal expression of MLH1 and MSH2 protein was determined by IHC using MLH1 and MSH2 antibodies. Normal and tumor DNAs were obtained from thirty CRC tissues that showed abnormal expression of MLH1 and MSH2 proteins by IHC. The MSI status was confirmed by PCR using five markers. RESULTS: Thirty tumors showed abnormal expression of MLH1 and MSH2 proteins by IHC, but only three tumors out of them were confirmed to have MSI by PCR. CONCLUSIONS: This result suggests that IHC with MLH1 and MSH2 antibodies does not seem to be a useful method to identify MSI in CRC, therefore PCR is required for detection of the MSI.
Adaptor Proteins, Signal Transducing ; Aged ; Carrier Proteins ; Colorectal Neoplasms/*genetics ; DNA-Binding Proteins/*analysis ; Female ; Humans ; Immunohistochemistry ; Male ; *Microsatellite Repeats ; Middle Aged ; MutS Homolog 2 Protein ; Neoplasm Proteins/*analysis ; Nuclear Proteins ; Polymerase Chain Reaction ; Proto-Oncogene Proteins/*analysis